The protective effect of fasudil against acrylamide-induced cytotoxicity in PC12 cells

Drug Chem Toxicol. 2020 Nov;43(6):595-601. doi: 10.1080/01480545.2018.1536140. Epub 2018 Dec 21.

Abstract

Acrylamide (ACR), a vinyl monomer that has multiple chemical and industrial applications, is a neurotoxic agent in human and animal. Fasudil is a potent Rho-kinase inhibitor which exhibits neuroprotective effects in some neuronal degenerative disorders. In this study, the potential protective effect of Fasudil on ACR-induced cytotoxicity in PC12 cells was evaluated. Our results showed that ACR increased the level of intracellular reactive oxygen species (ROS) and consequently upregulated the Bax/Bcl-2 ratio and significantly elevated the level of caspase-3 and 9 proteins in PC12 cells. Interestingly, pretreatment with Fasudil protected PC12 cells against ACR-induced toxicity mainly through the reduction of ROS production and modulation of proteins which involved in apoptosis pathway. Fasudil down-regulated the Bax/Bcl-2 ratio and the levels of caspase-3 and 9 proteins in cells exposed to ACR. In conclusion, the neuroprotective effect of Fasudil against ACR-induced toxicity in PC12 cells appears to be mediated through inhibition of ROS production and modulation of apoptosis.

Keywords: Acrylamide; Fasudil; apoptosis; neurotoxicity; rho-kinase inhibitor.

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives*
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • Acrylamide / toxicity*
  • Animals
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Cell Survival / drug effects
  • Cytoprotection
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology*
  • Neurotoxicity Syndromes / etiology
  • Neurotoxicity Syndromes / metabolism
  • Neurotoxicity Syndromes / pathology
  • Neurotoxicity Syndromes / prevention & control*
  • Oxidative Stress / drug effects*
  • PC12 Cells
  • Rats
  • Reactive Oxygen Species / metabolism

Substances

  • Antioxidants
  • Apoptosis Regulatory Proteins
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Acrylamide
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • fasudil